MS-275体外诱导膀胱癌细胞凋亡的机制探讨

目的研究组蛋白去乙酰化酶(HDAC)抑制剂MS-275对膀胱癌T24细胞的诱导凋亡作用,并初步探讨其分子机制。方法用MTT法检测MS-275对T24细胞的生长抑制作用,并观察其有效作用浓度,采用荧光显微镜及原位末端标记(TUNEL)法观察和检测MS-275对T24细胞的诱导凋亡作用,采用流式细胞仪(FCM)检测Bcl-2和Bax在细胞内表达的动态变化。结果 MS-275抑制T24细胞的半抑制浓度(IC50)为(5.21±0.61)μmol/L。4.0μmol/L的MS-275处理T24细胞后可观察到典型的凋亡形态学变化,且随着作用时间的延长,细胞凋亡率逐渐升高,同时引起Bcl-2及Bax的表达率分别下调和上调。结论 HDAC抑制剂具有体外诱导膀胱癌细胞凋亡的作用,其作用机制涉及Bcl-2及Bax表达的动态改变。

Explore on the mechanism of MS-275 inducing apoptosis in bladder cancer cell in vitro

Objective To investigate the apoptosis effect induced by MS-275, a histone deacetylase inhibitor, on bladder cancer T24 cell, and primarily discuss its molecular mechanism. Methods The cell growth inhibition was evaluated by MTT assay and the effective concentration was observed. The cell apoptosis was detected by fluorescence microscope and TUNEL mothed, respectively. The dynamic change of Bc1-2 and Bax expressing in T24 cell was measured by flow eytometry. Results The IC50 of MS-275 inhibiting the growth of T24 cell lines was （5.21±0.61） μmol/L. Typical apoptotic morphological change was observed in T24 cell treated by MS-275 at concentration of 4.0 μmol/L. Apoptotic rate were increased as time went on, with Bcl-2 down-regulated and Bax up-regulated. Conclusion HDAC inhibitor can induce apoptosis in bladder cancer cell in vitro and the change of expression of Bcl-2 and Bax is involved in its molecular mechanism.